Congenital metabolic diseases as a cause of acute illnesses in the neonatal period

Inborn errors of metabolism occurring in the neonatal period both comprise diseases with clinical onset immediately after birth and diseases with clinical onset after a symptom free interval. Organ damage caused by inherited metabolic diseases can occur already in utero or--depending on oral food intake--during the first postnatal days. Unselective screening methods are applied in neonatal mass screening programs for the early detection of metabolic diseases. In cases of unspecific clinical symptoms selective screening procedures may provide an effective diagnostic tool. If a patient with suspected metabolic disease dies, body fluids and organ biopsies should be preserved for further investigations. The establishment of a genotypspecific (enzyme) diagnosis needs time and cost consuming biochemical procedures. It is a prior condition for prenatal diagnosis in further pregnancies.     

Adrenocortical steroids in small-for-gestational-age term infants during the early neonatal period

We evaluated adrenocortical steroid concentrations at birth and during postnatal adaptation (2 h until 7 days) in 10 vaginally delivered term small-for-gestational-age (SGA) infants and 12 term appropriate-for-gestational age infants. Plasma aldosterone, 11-deoxycorticosterone, corticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone were longitudinally measured by specific RIA after Sephadex LH-20 chromatography. Mean aldosterone was significantly higher in SGA than in appropriate-for-gestational-age infants (2 h to 7 days; p less than 0.001). In SGA infants, cortisone and cortisol levels were significantly lower in umbilical artery (p less than 0.05), and all glucocorticoid levels were significantly lower 12 h after birth (p less than 0.05). Thereafter (24 h to 7 days), only 11-deoxycortisol levels remained significantly lower in SGA; corticosterone and cortisol levels were even higher (p less than 0.05) in SGA 24 h after birth. The data suggest that SGA infants maintain high aldosterone levels throughout the 1st wk of life. Low cortisol and cortisone levels in umbilical artery as well as low glucocorticoid levels at 2 h and/or 12 h compared to term appropriate-for-gestational-age infants may reflect either a less stressful postnatal adaptation or, more likely, a reduced adrenocortical synthesis in term SGA infants.     

Autoimmune involvement in Cushing syndrome due to primary adrenocortical nodular dysplasia

Cushing syndrome due to primary adrenocortical nodular dysplasia was diagnosed in two patients, aged 3 years 9 months and 9.5 years. Subsequently, adrenalectomy was performed and followed by steroid replacement. In both cases, the adrenals were normal or only slightly enlarged and showed adrenocortical nodular dysplasia histologically. Small lymphocytic infiltrates consisting of T-cells and class II MHC positive macrophages were present in adrenal specimens of both the patients. Samples of protein A sepharose purified serum immunoglobulins from both children stimulated adrenocortical DNA synthesis and cortisol production in cultured guinea-pig adrenal segments in vitro in a dose dependent fashion. Adrenal stimulating immunoglobulins were also demonstrated in serum specimens of both patients' mothers. However, none of them had overt signs of adrenal disease. Our data support the view that autoimmune mechanisms may be involved in primary adrenocortical nodular dysplasia.     

Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period

Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.     

Macleod's syndrome as a cause of recurrent pneumonia in a child]

Macleod's syndrome is a rare cause of recurrent pneumonia in children. A case report is described and the diagnostic utility of chest roentgenogram and CAT is emphasized.     

Pustular dermatoses in the neonatal period]

The diagnosis of pustular dermatosis occurring during the first months of life is usually based on clinical findings. However, some cases may require a few simple investigations including cytological studies, cultures, and skin biopsies. The most common causes of infectious pustular skin lesions include bacterial infections, which may be septicemic (with Listeria as the leading causative agent) or initially localized (staphylococcus); viral infections (varicella, herpes); fungal infections, i.e., candidiasis (congenital or neonatal) or the very recently described form of pustulosis due to Malassezia furfur; or parasitic (scabies). The main benign transient neonatal forms of pustulosis include infantile acropustulosis (for which the relationship with scabies is discussed), toxi-allergic erythema, transient pustular melanosis, and neonatal acne. Lastly, rare causes of neonatal pustulosis are reviewed. The need for investigating every neonate with skin pustules for an infectious disease, especially due to a bacterium, is emphasized.     

A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism.

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.     

Cushing syndrome as a presenting symptom of renal tumors in children

Cushing syndrome as the presenting symptom of a malignant renal tumor in children is rare. We report the first case of paraneoplastic Cushing syndrome due to a Wilms tumor, in which clinical and biological signs of hypercortisolism regressed during preoperative chemotherapy. Additionally, we reviewed the literature on paraneoplastic Cushing syndrome secondary to pediatric renal tumors. Pediatr Blood Cancer 2009;53:211–213. © 2009 Wiley‐Liss, Inc.     

Hepatopulmonary syndrome associated with nodular regenerative hyperplasia after liver transplantation in a child

HPS is a significant complication of portal hypertension in children with chronic liver disease and is an established indication for LT. It is characterized clinically by the triad of pulmonary vascular dilatation causing hypoxemia in the setting of advanced liver disease. NRH, a cause of non‐cirrhotic portal hypertension, is characterized by diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Development of NRH and HPS in pediatric LT recipients has not been reported, although occasional cases have been reported in adult LT recipients. In this report, we discuss a case of a three‐yr‐old male who developed HPS, two yr after LT. Pulmonary and cardiac causes for hypoxemia were ruled out by appropriate investigations including a chest X ray, echocardiogram, cardiac catheterization, and a CT angiographic study. The diagnosis of HPS was confirmed via bubble echocardiogram that demonstrated intrapulmonary shunting. Open liver biopsy revealed marked NRH. The patient underwent liver retransplantation that resulted in complete reversal of his pulmonary symptoms and normal oxygen saturations within three months after LT.     

Cushing's syndrome caused by nodular adrenal hyperplasia in children with McCune-Albright syndrome.

McCune-Albright syndrome consists of fibrous dysplasia of bone, café-au-lait skin pigmentation, and endocrine dysfunction (usually precocious puberty). Other endocrine abnormalities occur in a minority of patients, and of these, Cushing's syndrome is the least often recognized. We present 5 children (4 girls) with features of McCune-Albright syndrome who had Cushing's syndrome in the infantile period (<6 months). In 2 children spontaneous resolution occurred, but the remaining 3 required bilateral adrenalectomy. In addition, all 4 girls have experienced precocious puberty, and 3 children demonstrated radiologic evidence of nephrocalcinosis. Understanding of the underlying defect causing McCune-Albright syndrome emphasizes the importance of searching for other endocrine dysfunction in these children.     

Parameningeal cervical rhabdomyosarcoma in the neonatal period]

A case of parameningeal cervical rhabdomyosarcoma with severe bone destruction is reported in a 3 month-old infant; symptoms were present at birth. The treatment consisted of exclusive intensive chemotherapy. The outcome was favourable with complete tumor regression and vertebral bone reconstruction. The child was on complete remission without sequellae two years later.     

Hypophosphatasia as a rare cause of neonatal seizures

Severe forms of hypophosphatasia due to loss-of-function in the ALPL gene may present with diverse neurological problems including pyridoxine-responsive seizures. We present a short report of pyridoxine-responsive neonatal seizures. Due to severe osteopenia with unmeasurable levels of alkaline phosphatase, targeted genetic screening was performed and two pathogenic variants in the gene for the nonspecific alkaline phosphatase confirmed the diagnosis of hypophosphatasia. We would like to emphasize the importance of considering infantile hypophosphatasia in the differential diagnosis of pyridoxine-responsive seizures with concomitant low alkaline phosphatase level and bone pathology, especially with the new treatments becoming available in the future.     

Hepatic nodular hyperplasia in a boy with Alagille syndrome: CT and MR appearances

A boy with Alagille syndrome complicated by hepatic nodular hyperplasia (HNH) is reported. During pre-transplantation evaluation, CT and MRI revealed a large hepatic lesion with multiple small nodular lesions. Angiography demonstrated a large hypervascular lesion and CT arterial portography (CTAP) showed a portal perfusion defect corresponding to the lesion. CTAP also revealed large portal vein branches running through the lesion. Although hepatocellular carcinoma is known to accompany Alagille syndrome, HNH should also be considered when large vessels running through the lesion are demonstrated. Received: 7 March 2000 Revised: 3 October 2000 Accepted: 5 March 2001     

Nuchal cord as a cause of neonatal anemia

Nuchal cord was documented in 437 neonates consecutively admitted to the newborn nursery at The University of Texas Medical Branch Hospital, Galveston. The prevalence of anemia in the nuchal cord group (venous hemoglobin level of less than 13.2 g/dL or hematocrit of less than 39.2%) was compared with that in a control group. None of the controls was anemic. Five of 27 neonates with tight nuchal cord and four of 30 with loose nuchal cord were anemic. Anemia in the tight nuchal cord group was usually observed early, and in three infants was manifest by hypotension, necessitating transfusion. Anemia associated with loose nuchal cord occurred later and was asymptomatic. This study emphasizes the increased risk of anemia associated with nuchal cord and demonstrates the need for hemoglobin and hematocrit determinations in neonates with this obstetrical complication.     

The diagnosis of Dubowitz syndrome in the neonatal period — a case report

We present an infant with Dubowitz syndrome diagnosed at birth and followed for 2 years. Presence of the syndrome was suspected at birth on the basis of the anthropometric data and peculiar facial appearance. However, during the follow-up period some changes in the appearance have taken place. It is suggested that the neonatal anthropometric measurements are important diagnostic criteria for Dubowitz syndrome.Abbreviation OFC head circumference