The clinical features associated with Donohue syndrome are mostly present since birth, although they may show considerable individual variation  .
Growth delays are present in a majority of the infants affected, with low birth weight and a failure to thrive being amongst the common manifestations. These infants are often emaciated, with underdeveloped muscles and/or bones. Bone age and maturation are delayed as compared to their peers.
A characteristic craniofacial structure helps in identifying infants with leprechaunism. Affected infants may show a wide variety of distinctive facial features such as underdeveloped, huge, low-set ears; macrostomia with thickened lips; hypertelorism; microcephaly; and a flattened nose.
A vast majority of infants also present with certain dermatological features, with the skin being abnormally thickened (pachyderma) and pigmented (acanthosis nigricans). An absence of subcutaneous body fat, hirsutism, and dysplastic nails may also be seen.
Endocrine disturbances form the other crux of the clinical abnormalities seen in patients with Donohue syndrome. Hyperinsulinemia is a common finding in such infants, owing to the absence of functional insulin receptors due to homozygous/ heterozygous mutations in the INSR gene   . Postprandial hyperglycemia and fasting hypoglycemia are frequently observed. Affected females may have cystic ovaries and an abnormally enlarged clitoris/ breasts, while males may be afflicted with an abnormally large penis. Cardiac lesions such as hypertrophic cardiomyopathy may also be observed.
Other abnormalities that have been observed in infants with leprechaunism include recurrent infections, abnormalities of the intellect and unusually large hands and feet. Abdominal complaints such as a distended stomach, cholestasis, iron accumulation in the liver and umbilical/ inguinal hernia have also been seen in some patients.
Infants with Donohue syndrome are reliably diagnosed by identifying the characteristic clinical features, along with biochemical and genetic evaluations to confirm the same.
The diagnosis of leprechaunism is confirmed by the presence of mutations in the insulin receptor gene (INSR 19p13.3-p13.2) via a polymerase chain reaction (PCR). A real-time qualitative PCR is usually preferred, although semi-quantitative and quantitative evaluations are now available as well. This genetic analysis may be performed either before or after birth. DNA samples prenatally are collected via amniocentesis. Genetic sequencing techniques thus, aid in diagnosing and counseling mothers with affected babies in their current and/ or subsequent pregnancies.
Other disorders that arise from INSR gene mutations include the type-A insulin resistance syndrome and the Rabson-Mendenhall syndrome and these form the differential diagnosis of leprechaunism. All these diseases represent a continuous clinical spectrum, with Donohue syndrome the most severe (patients usually die by the age of 2 years) and Rabson-Mendenhall syndrome being relatively moderate in severity  . Type-A insulin resistance syndrome is usually benign, with patients being diagnosed during adolescence.