ANSWERS TO CASE STUDY: CAN YOU DIAGNOSE THIS CASE?

Answers

(a) Maturity inset diabetes of the young (MODY)

(b) Molecular genetic analysis

(c) Subcutaneous insulin

BRIEF EXPLANATION:

The WHO defines diabetes as venous plasma glucose 7 mmol/l or more fasted or 11.1 mmol/l or more unfasted on

more than one occasion. Most cases (99%) are type 1 diabetes, but a number of other types of diabetes are now recognised in children. These subtypes are rare, and correct diagnosis is important as their management and clinical course differ.

Clinical features and laboratory investigations help to differentiate the various types.

Type 1 diabetes is an autoimmune disorder characterised by beta cell destruction and dependence on insulin. Pancreatic antibodies are often present at diagnosis (GAD-65 25–76%, islet cell antibodies 68–79%), though absence of antibodies does not exclude type 1 diabetes. Measurement of GAD antibodies may be useful when there is diagnostic doubt. Ketonuria is often present at diagnosis and there is often a family history of diabetes or other autoimmune conditions.

Type 2 diabetes is characterised by insulin resistance and is associated with obesity. There may be other features of the metabolic syndrome (acanthosis nigricans, hypertension, hyperlipidaemia) and a family history of diabetes. The child may be asymptomatic or have features of polyuria and polydipsia. Ketonuria may be present.

MODY is a heterogeneous group of disorders caused by defects in single genes resulting in beta cell dysfunction. It is characterised by beta cell dysfunction, young onset (o25 years) and autosomal dominant inheritance. Obesity is not a feature. The diagnosis should be considered in non-obese patients with a two- or three-generation history of diabetes on one side of the family. Molecular genetic analysis identifies the gene defect.

Prognosis and management depend on the defect. Some patients do not require insulin.

The term ‘latent autoimmune diabetes’ refers to a group of patients who have antibodies consistent with type 1 diabetes but whose condition initially behaves as non-insulin requiring.

Diabetes is associated with a number of other disorders (e.g. cystic fibrosis).

Diabetes insipidus is also characterised by polyuria, polydipsia and weight loss, but is due to a deficiency of (central diabetes insipidus) or renal insensitivity to (nephrogenic diabetes insipidus) vasopressin (antidiuretic hormone). It is not associated with hyperglycaemia, glycosuria or raised HbA1C. Clinically, polydipsia becomes a prominent feature, with the patient waking at night to drink and drinking any available fluid. If diabetes insipidus is suspected, investigations should include paired serum and urine osmolality and consideration of a water deprivation test to differentiate between the two causes.

Management at diagnosis – unwell or ketotic children should be started on insulin at diagnosis. The diagnosis and management can then be reviewed if there are atypical features of diabetes (low insulin requirement, no subsequent ketonuria, strong family history of non-type 1).

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