CHEM-643 INTERMEDIARY METABOLISM
Problem Set 7, In class October 20, 1994
Sick Kids with an Unusual Organic Aciduria
Consider your group to be an expert consulting team that takes pride
in diagnosing metabolic diseases based on the abnormal organic acids
excreted in a patient's urine. Over the years, for good reason,
doctors from far and wide have come to rely on your team to solve
their difficult cases. Typically they want to know what enzyme is
defective and what therapies might ameliorate or eliminate the
pathological consequence of various inborn errors of metabolism. Your
team sees each new case as an intellectual challenge, but the greatest
satisfaction comes from being able to save lives or improve the
quality of life often through simple changes in a patient's diet.
One day a pediatrician presents your team with an especially puzzling
pair of similar cases which she has never seen described in the
literature. Although she respects your group's talents and certainly
wants to help her patients, privately she is entertained by the idea
that these cases will finally stump you. How, she asks, can a single
enzyme defect cause the accumulation of the organic acids she
Description of the First Patient
The patient was a white female two years and nine months old, the
product of a full-term pregnancy and delivery. At three months of age
she began to have generalized seizures that occurred approximately 10
times per day and were unresponsive to phenobarbital. The seizures
persisted and at 14 months an eczematoid rash and alopecia developed,
progressing to involve the entire head, including eyebrows and
eyelashes. At 16 months of age the patient was first noted to have
metabolic acidosis with a serum bicarbonate less than 15 mmol per
liter. By 21 months she had ataxia, severe enough to interfere with
her ability to walk. At 22 months she was first noted to have an
elevated concentration of lactic acid in plasma. At 31 months she had
severe keratoconjunctivitis requiring hospitalization. The patient's
developmental progress was normal until seven months of age, when her
development was delayed. From seven to 37 months her developmental
age progressed by only 22 months. Throughout this period she received
a normal diet and at no time was fed raw eggs. Her physical
appearance at 31 months of age is shown in Figure 1. (See original
reference.) She was profoundly acidotic, with plasma lactic
acid concentration of 41 mg per deciliter (4.6 mmol per liter) and
pyruvate concentration of 2.7 mg per deciliter (0.31 mmol per liter).
She was irritable, somnolent, and in moderate distress, with marked
alopecia, keratoconjunctivitis, and perioral stomatitis.
[Reprinted from the New England Journal of Medicine 304:817--820
Description of the Second Patient
The second patient was a two-year old boy whose profile of urinary
organic acids (Table 1) was similar to those of patient 1.
Table 1. Urinary Excretion of Organic Acids (micromol/mg
creatinine) by Patient 2.
|24 Hour Urine Volume (ml)
Postulate a single enzymatic defect that could explain the presence of the various
organic acids in the above table.
Suggest a therapy that might reduce or eliminate the symptoms.
643prob7.doc HBW 10/3/94
Last updated Feb. 24, 1997.
Copyright Univ. of Delaware, 1997.