Juvenile acid maltase deficiency presenting as paravertebral pseudotumour

In addition to the infantile lethal form of glycogen storage disease with cardiomyopathy (GSD Type IIa, Pompe disease) 1,4 glucosidase or acid maltase deficiency has been reported in a few children and adults (GSD Type IIb or IIc) erroneously thought to have muscular dystrophies. The clinical heterogeneity of the muscle involvement in these latter cases is illustrated in a 12-year-old boy presenting with a right lumbar mass, growth retardation, muscular weakness including difficulty in walking, and marked elevations of muscle and liver enzymes. Light-and electron-microscopic examination of specimens from the lumbar mass, apparently normal skeletal muscle and liver, showed typical changes consistent with the biochemical and enzymatic features of acid maltase deficiency. GSD Type IIb and IIc are more frequent than suspected, may present as local pseudohypertrophy and should be considered in patients with progressive muscle disease and abnormal serum enzymes.Abbreviations GSD glycogen storage disease - SGOT serum glutamic oxaloacetic transaminase - SGPT serum glutamic pyruvate transaminase - LDH lactic dehydrogenase - CPK creatinine phosphokinase - MUG 4-methyl-umbelliferyl-alphad-glucoside     

Infantile form of muscle phosphofructokinase deficiency in a premature neonate

Muscle phosphofructokinase (PFK) deficiency is a rare autosomal recessive disease. We report the case of a preterm female infant who was diagnosed with the infantile form of phosphofructokinase deficiency due to a lack of PFK activity in her muscles, manifesting at a corrected age of 1 month as floppy infant syndrome, congenital joint contracture, cleft palate and duplication of the pelvicalyceal system. She died at a corrected age of 6 months due to respiratory failure. We further reviewed other infantile cases in the literature. Congenital hypotonia (78.6%), arthrogryposis (64.3%) and other systemic involvement including encephalopathy (35.7%) and cardiomyopathy (21.4%) are common presentations of the infantile form of PFK deficiency. The overall survival rate of the infantile form is low. The early recognition of multiple system involvement is essential to provide better clinical care for infants with the infantile form of PFK deficiency.     

Neonatal nemaline myopathy presenting with multiple joint contractures

A sporadic case of the rare and most severe neonatal form of nemaline myopathy is reported. Intrauterine manifestation included reduced fetal movements and breech position with a normal amount of amniotic fluid. After delivery by Caesarian section at 34 weeks of gestation the infant boy, who was not asphyctic, failed to establish spontaneous breathing and required immediate intubation and ventilation. Marked muscular hypotonia and weakness persisted and reflexes remained absent. Hip dislocation, joint contractures, absent palmar creases, prominent lateral palatal ridges and cryptorchidism were interpreted as consequent to prenatal paralysis. The boy died after 5 h due to hyaline membrane disease and meconium aspiration. At autopsy the skeletal muscles were found to be hypoplastic. The muscle fibres contained numerous rods, a typical finding of nemaline myopathy.Nemaline myopathy should be considered in fetuses and newborns with multiple joint contractures, severe muscular weakness and respiratoy insufficiency.     

Progressive Muscular Dystrophy in Infancy

Clinical features of 11 cases of muscular dystrophy in infancy were discussed. From the detailed symptomatological analysis of the 11 patients we reported here, we found two subgroups of infantile muscular dystrophy. There were 6 cases of congenital cerebro-muscular dystrophy (Fukuyama) and 5 cases characterized by comparatively late onset, no sexual preference, proximally dominant muscle wasting, infrequence of associated joint contractures, normal facial muscle and no mental deficiency. The characteristics of this latter group in infantile muscular dystrophy are similar to those of limb-girdle muscular dystrophy. It is suggested that some of the patients with limb-girdle type of muscular dystrophy may have its onset in infancy.     

Amylopectinosis disease isolated to the heart with normal glycogen branching enzyme activity and gene sequence

We report a 17-month-old female patient with a rare cause of cardiomyopathy secondary to accumulation of amylopectin-like material (fibrillar glycogen) isolated to the heart. Evidence of amylopectinosis isolated to cardiac myocytes in this patient was demonstrated by histology and electron microscopy. Glycogen content, glycogen branching enzyme (GBE) activity, as well as phosphofructokinase enzyme activities measured in liver, skeletal muscle, fibroblasts and ex-transplanted heart tissue were all in the normal to lower normal ranges. Normal skeletal muscle and liver tissue histology and GBE activity, normal GBE activity in skin fibroblasts, plus normal GBE gene sequence in this patient exclude the classical branching enzyme deficiency (type IV GSD). We believe that this is an as yet uncharacterized and novel phenotype of GSD associated with cardiomyopathy, in which there is an imbalance in the regulation of glycogen metabolism limited to the heart.     

Deletions in the spinal muscular atrophy gene region in a newborn with neuropathy and extreme generalized muscular weakness.

A newborn presented with respiratory insufficiency requiring artificial ventilation, inability to swallow, lack of spontaneous movements including the facial muscles, and areflexia. Nerve conduction velocities were not recordable. Molecular analysis showed a homozygous deletion in the spinal muscular atrophy (SMN) gene region on chromosome 5q. Pathological and neuropathological examination revealed a normal number of anterior horn cells, hypomyelinated axons in peripheral nerves and some atrophy of skeletal muscle fibres in combination with sarcoplasmic glycogen accumulation. This observation illustrates that severe congenital neuropathy can result from deletions in the SMN gene.     

Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features.

Adenylosuccinase deficiency is an autosomal recessive inherited defect of purine synthesis. In enzyme deficient patients, two normally undetectable compounds, succinylaminoimidazole carboxamide riboside and succinyladenosine, accumulate in urine, cerebrospinal fluid and, to a minor extent, in plasma. Analysing 150 highly selected urine specimens from patients with unidentified neurogenerative disorders we discovered the first two German cases of adenylosuccinase deficiency. The deficiency causes moderate to severe mental retardation, often accompanied by epileptic seizures and/or autistic features, and is occasionally associated with growth retardation and muscular hypotonia. Of the two German cases we present here, one patient fits into the clinical picture outlined by previous reports. The other patient, however, shows a pattern of symptoms so far undescribed: severe early infantile epileptic encephalopathy with reduced myelination. On mutation analysis this patient is the first to reveal a 39 base pair deletion in the adenylosuccinase gene in contrast to the point mutations detected in previous cases. Adenylosuccinase deficiency may be an underdiagnosed metabolic disorder with variable expression. This should be taken into consideration in patients with unclassified neurological conditions.     

Liver glycogen synthase deficiency: A rarely diagnosed entity

Three children from two German families are described and the observations compared with the previously published three families comprising eight patients. The two index cases presented with morning fatigue, had ketotic hypoglycaemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency and absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and night-time feedings of suspensions of uncooked corn (maize) starch. The discovery of oligosymptomatic and asymptomatic siblings suggests that there are more persons with undiagnosed hepatic glycogen synthase deficiency.     

Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome

We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.     

Glycogen Accumulation in the Pars Recta of the Proximal Tubule in Fanconi Syndrome

We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.     

330例遗传代谢性肝病患儿病因学分析

目的分析遗传代谢性肝病的病因。方法回顾分析2013年1月至2019年12月收治的遗传代谢性肝病患儿的临床资料。结果共330例遗传代谢性肝病患儿,男性205例、女性125例,发病年龄1月龄~14岁。病因有50余种类型,依次为Citrin缺陷病(120例,36.36%)、肝豆状核变性(WD,53例,16.06%)、糖原累积症(GSD,52例,15.76%)、遗传性高胆红素血症(25例,7.58%)、Alagille综合征(16例,4.85%)和进行性家族性肝内胆汁淤积症(PFIC,10例,3.03%)等。患儿以胆汁淤积、氨基转移酶升高为主要首发表现,其中胆汁淤积188例(56.97%)、氨基转移酶升高127例(38.48%)。1岁内发病者181例(54.85%),以Citrin缺陷症(120例)、GSD(10例)、PFIC(7例)、Alagille综合征(7例)和Dubin-Johnson综合征(6例)为主;1岁及以上发病149例(45.15%),以GSD(42例)和WD(52例)为主。结论遗传代谢性肝病病因复杂,临床上应结合发病年龄和临床表现进行诊断分析。     

Muscular form of glycogenosis type II (Pompe's disease).

An 11-year-old boy who was previously thought to have progressive muscular dystrophy was studied clinically, biochemically, and histologically. He was seen initially with an amyotonic syndrome with no clinical evidence of heart disease. Light and histochemical examination showed vacuolar degeneration and abnormal accumulation of glycogen in the muscular fibers. Electron microscopy showed aggregates of glycogen granules surrounded by a well-defined membrane, as in previously reported cases of type II glycogenosis. Enzymatic study disclosed that acid alpha-glucosidase was deficient in muscle, liver, and heart tissue, although neutral alpha-glucosidase was present within normal ranges. Measurement of acid and neutral alpha-glucosidase activity in muscle from the patient and his sisters and in urine from them and their parents indicated that his sisters are heterozygotes and his parents probably are heterozygotes. The disease was transmitted as an autosomal-recessive trait.     

57例儿童重度臀肌挛缩的诊治分析

目的 探讨小儿重度臀肌挛缩的诊断依据以及治疗方法。方法 回顾性分析57例儿童重度臀肌挛缩的病理和临床特点以及手术方法上与常见型臀肌挛缩的区别。手术强调彻底松解所有影响髋关节活动的肌肉和组织。故不仅要常规切断挛缩的臀大肌，髂胫束与阔筋膜张肌。更关键的是一定要同时切断夹杂在臀中、臀小肌内的挛缩肌束以及挛缩增厚的髋关节囊后半部分，有些甚至需要切断挛缩的梨状肌。结果 57例114侧全部经手术治愈。术后少部分病例有下肢不等长，关节弹跳等并发症。但经1年—2年正确功能训练后，均恢复正常。本组病例无再手术者。结论 重度型儿童臀肌挛缩其临床症状、病理改变较常见型更严重、更广泛。手术彻底松解所有影响髋关节活动的挛缩组织，即能达到较好的效果。     

Reversible mitochondrial myopathy with cytochrome c oxidase deficiency.

Two siblings, a boy and a girl born in a nonconsanguineous marriage, presented with a similar clinical course. Sucking and breathing difficulties appeared within a few weeks of birth. Clinical examination revealed profound muscular hypotonia, hepatomegaly, increased serum creatine kinase activities, and lactic acidosis. Both infants were treated with gavage feeding, the boy also needing ventilatory support. Clinically they improved gradually. Now, the boy aged 4 years and the girl aged 28 months are free of clinical signs. Muscle biopsy specimens taken at 3 months showed, in both, ragged red fibres, abnormal mitochondria, and reduced cytochrome c oxidase (COX) staining. Biochemical analysis showed COX activity to be reduced to about 25% of the normal mean. The second biopsy specimen from the boy at 16 months was normal on morphological examination, but the girl's second specimen at 13 months still showed abnormal features. These cases are examples of the rare benign reversible COX deficiency. Early diagnosis is crucial to provide intensive treatment until spontaneous clinical improvement appears.     

Cardiac involvement in glycogen storage disease type III

Twenty patients with enzymatically proven glycogen storage disease type III (GSD III) aged 3–30 years underwent cardiological evaluation. Seventeen showed subclinical evidence of cardiac involvement in form of ventricular hypertrophy on ECG. Of 16 patients in whom an ECG examination was performed, 13 had abnormal echocardiographic features. Only 2 patients had cardiomegaly on X-ray. The cardiac findings in 1 of the patients, a 25-year-old female with clinically evident cardiomyopathy are described in detail. In view of our findings, patients with established GSD III, should not only be investigated regarding their muscular involvement, but should also undergo a detailed evaluation of their cardiac status.Abbreviation GSD glycogen storage disease     

Effects of maternal diabetes on the development of carbohydrate-metabolizing enzymes, glycogen deposition and surface active phospholipid levels in fetal rat lung

Streptozotocin-induced maternal diabetes has been shown to alter developmental patterns of carbohydrate-metabolizing enzyme activities, glycogen deposition and surfactant levels in late fetal rat lung in a tissue-specific manner, as follows: (a) marked reduction in glycogen synthase a activity, due to aberrant interconversion between active and inactive forms of the enzyme; less glycogen was thus accumulated; (b) lowered activities of hexokinase, phosphofructokinase and pyruvate kinase at term; (c) reduced disaturated phosphatidylcholine (surfactant) concentrations. The diminished synthesis and accumulation of glycogen and glycolytic capacity in the lungs of fetuses of diabetic mothers has been related to reduction in surfactant level, which underlies respiratory distress syndrome frequently encountered in neonates of diabetic pregnancies.     

Glycogenosis type I

OBJECTIVE: To o present up-to-date knowledge about Glycogen storage disease type I (GSD-type I) - a disease caused by the deposit of glycogen resulting from the deficiency of the enzyme glucose-6- phosphatase - and to provide the pediatricians with the necessary information for a precocious diagnosis and an adequate conduct for those cases where this metabolic disturbance is present. METHODS: Through Medline, the most significant articles published during the last 20 years were selected from national and international journals of medicine, with special attention to dietary treatment of glycogen storage disease type I. RESULTS: The metabolism of glycogen and the metabolic consequences of glycogen storage disease type I were discussed, especially hypoglycemia, the principal metabolic disturbance of the disease. The clinical and laboratory findings are described together with the histopathology. The use of uncooked cornstarch and enteral carbohydrate infusion are the means used for the maintenance of normoglycemia. The control of hyperuricemia, hyperlipidemia and platelet disorders are other aspects of the treatment as well as the prevention of infections and the use of G-CSF for glycogen storage type Ib. Hepatic transplant and its principal indications are commented on. Hepatic adenomae, which always have the potential of malignant transformation, are the results of incomplete treatment. CONCLUSIONS: Although it occurs rarely, glycogen storage type I is an important cause of volumous hepatomegaly which is associated with hypoglycemia among the infants. The dietary treatment of this illness has significantly altered the clinical course and has improved the prognosis. Therefore it is indispensable that the general pediatrician should be familiar with the diagnosis of this clinical state so as to act rigorously in favor of the dietary control.     

Inherited metabolic diseases in the sudden infant death syndrome.

All sudden, unexpected infant deaths presenting during a two year period within a defined geographical area in Avon and north Somerset were investigated for inherited metabolic disease. Of 95 deaths, 88 were classified as cases of sudden infant death syndrome (SIDS). In addition to the normal postmortem investigations, samples of cerebrospinal fluid, urine, vitreous humour, and skin were collected for metabolic studies. No abnormal organic acid metabolites were found in the fluids from the 88 cases of SIDS. Fatty acid oxidation was assessed in skin fibroblasts from 70 cases of SIDS, but no examples of medium chain acyl CoA dehydrogenase (MCAD) deficiency were found. One case with abundant glycogen in the liver was subsequently diagnosed as having glycogen storage disease type 1c. These findings suggest that the incidence of MCAD deficiency and other metabolic diseases in SIDS is much lower than previously claimed.     

Biochemical characteristics of "young" and "old" erythrocytes of the newborn infant.

Cord blood samples from ten term infants were fractionated into populations of young and old erythrocytes and compared with cells prepared in a similar fashion from eight normal adults. The old cell fraction from the newborn infants had very low phosphofructokinase activity and did not display the usual decline of activity of the enzymes phosphoglycerate kinase and enolase. In addition, the old cells from the newborn infants demonstrated impaired glucose consumption, which, upon analysis of the pattern of glycolytic intermediates, appeared to be a result of the phosphofructokinase deficiency. These findings suggest that cells produced earlier in gestation possess the developmental characteristics of fetal blood to a more significant degree and that these biochemical alterations may produce functional impairment.