Perween Mufti  ( Department of Paediatrics, Aga Khan University Hospital, Karachi. )
Iqbal Ahmed  ( Department of Paediatrics, Aga Khan University Hospital, Karachi. )

A total of 21 patients were admitted to Aga Khan University Hospital with suspected congenital hyperammonemias during the period 1989 to 1992, 11 with acidosis and 10 without acidosis. Prominent clinical manifestations included positive family history (76%), onset in the first week of life (67%) and neurological manifestations (76%). Of patients with hyperammonemia and acidosis, 4 had severe metabolic acidosis with anion gap of 3OmEq/L and above. Of patients with hyperammonemia without acidosis, 4 had ammonia level ranging from 1600-2000ug/dl. Diagnosis was confirmed in only 1 patient and that was also done abroad. Overall mortality was 71%. These disorders are not uncommon in our country and should be suspected in all Infants with above clinical or biochemical abnormalities (JPMA 43:232, 1993).

Inborn errors of metabolism are a group of disor­ders which result from partial or complete absence of enzymes involved in biochemical reactions within the cells. This leads to both abnormal synthesis as well as ketabolism of metabolites. Most of these metabolites are neurotoxic and may cause death in early neonatal period or severe neurological disability. There are about 60 inherited metabolic disorders which can present in the neonatal period^1,2. Number of these can be treated successfully if suspected and diagnosed early. Galac­tosemia³, phenylketonuria⁴, homocystinuria^5,6, methyl­malonic aciduria^6,7 and congenital hyperammonemia^8-10 are group of disorders for which treatment is available. This study reports different types of disorders with hyperammonemia, their clinical manifestation and out­come.

From January, 1989 to December, 1992, a review of charts of all infants whose laboratory evaluation or clinical manifestation were suggestive of congenital hyper ammonemias were included in the study. Clinical manifestations and laboratory evaluation, which helped in the diagnosis are shown in Tables I and II^1,2,11-13.

Twenty one (11 with and 10 without metabolic acidosis) patients, suspected of having hyperammonemia (Table III).

Patients with isovaleric acidemia and non­ketotic hyperglycinemia diagnosed elsewhere were fol­lowed at AKU. Ml infants were admitted to neonatal intensive care unit/intensive care unit.

Table IV shows the treatment given to these infants.^{8,10,12,14,15}

Table V shows major clinical manifestation. Prominent fntures included positive family history (76%), onset n the first week of life (67%) and neurologi­cal manifestation (76%).


Table VI and VII show laboratory evaluations of these patients. All 3 patients suspected of having Maple syrup urine disease (MSUD) had abnormal excretion of isoleucine. 1/3 infants also had Maple syrup body odour. Ammonia level was normal in 2/3 infants. Of 6 patients suspected of organic acidemia, five died. Four had severe metabolic acidosis with aniongap of> 3OmEaJl. Patient # 7 was included in the study because there was strong family history of sibling deaths, compensated metabolic acidosis and high sepsis. This infant is alive and thriving. Urinary chromatography was not helpful in any of these cases. Among infants with hyperammonemia without acidosis, 4 had ammonia level ranging from 1600-nearly 2000 ug/dl. One of these infants also had terminal metabolic acidosis with pH of 6.9 and an aniongap of 25 mEq/I (Patient # 14,16,17,21). Patient # 21 was first seen at 8 months of age with recurrent episodes of intermittent vomiting and drowsiness and then at one year of age. This time his drowsiness progressed to coma. Ammonia level prior to death was 727 ug/dl. Urea cycle defect was suspected in all 5 infants. The other 4 infants were also suspected of having urea cycle defect. Patient # 13 was twin brother of patient # 16; he died at 2 months of age in a comatosed state. Unfortunately NH3 level was not documented at this time. Patient # 18 presented with failure to thrive. vomiting and diarrhoea. He weighed 1.9 kg at 2 months of age. This child was lost to follow-up. Patient # 19 developed seizures at I month of age. Three of her siblings died of similar complaints. Patient # 14 was aged 4 years who had intermittent episodes of unconsciousness, was lost to follow-up. Infant with non-ketotic hyperglycinemia was 2 year old female who presented to ER with hypoglycemic coma, and died on the same day.

Table VIII shows the outcome. 15/21 (7 1%) infants died. Three infants were lost to follow-up.

This is undoubtedly large group of patients with congenital hyperammonemia seen at AKU which is one of the largest teaching hospitals in this country. One of the major problems encountered here was confirmation of diagnosis which could not be done because of non existence of diagnostic facilities needed for this purpose. However, inspite of this, these conditions were suspected on clinical symptom and tests described in Table II. Overall mortality was extremely high. In patients with less severe clinical presentation proper manage­ment led to improvement. It is felt that because of consanguineous marriages in this country these problems may not be infrequent and there is a great need for establishing diagnostic facilities to confirm diagnosis, institute early treatment for better outcome and counsell­ing parents. It is important to make the diagnosis for the sake of parents who have every right to know why their infants had died and for the purpose of genetic counsell­ing.

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